It has been postulated that the immunological phenotype of a leukemic lymphoblast represents the stage at which differentiation is blocked. The normal counterpart of the common acute lymphoblastic leukemia (cALL) cell is thought to be a lymphoid precursor present in normal marrow from children and in regenerating marrow after bone marrow transplantation or cessation of suppressive chemotherapy. Like cALL cells, those cells express Ia antigens, terminal deoxynucleotidyl transferase enzyme and the common ALL antigen. At present, it is unclear whether the cALL reactivity of these normal marrow cells and cALL blasts is due to the presence of identical, related or unrelated proteins in the membranes of these cells. A specific aim of this investigation, therefore, is the chemical characterization of the cALL antigen(s) from both normal and leukemic cells. This will include NH2-terminal analysis, using microsequencing techniques and carbohydrate analysis. The proteins will be isolated for structural studies by immunoadsorption and HPLC techniques, using commercially available monoclonal antibody to the cALL protein (J5). Structural studies of the cALL protein(s) isolated from different cell populations should prove unequivocally the identity or relatedness of these antigens on leukemic and normal lymphoid cells. If different, we will attempt to determine what changes, if any, are associated with malignancy. This distinction between a lymphoid differentiation antigen and a leukemia specific antigen is critical both for understanding the transformation process and for clinical considerations such as the future use of antibodies as therapeutic agents. Additional benefits will be the further examination of the distribution of the cALL antigen using monoclonal antibodies, and a possible insight into the function of the cALL protein by knowledge of its structure.